Hydrophobic surfaces are known to adsorb and unfold proteins, a process that has been studied only
for a few proteins. Here we address the interaction of b2-microglobulin, a paradigmatic protein for the
study of amyloidogenesis, with hydrophobic surfaces. A system with 27 copies of the protein
surrounded by a model cubic hydrophobic box is studied by implicit solvent molecular dynamics
simulations. Most proteins adsorb on the walls of the box without major distortions in local geometry,
whereas free molecules maintain proper structures and fluctuations as observed in explicit solvent
molecular dynamics simulations. The major conclusions from the simulations are as follows: (i) the
adopted implicit solvent model is adequate to describe protein dynamics and thermodynamics;
(ii) adsorption occurs readily and is irreversible on the simulated timescale; (iii) the regions most involved
in molecular encounters and stable interactions with the walls are the same as those that are important
in protein–protein and protein–nanoparticle interactions; (iv) unfolding following adsorption occurs at
regions found to be flexible by both experiments and simulations; (v) thermodynamic analysis suggests a
very large contribution from van der Waals interactions, whereas unfavorable electrostatic interactions
may occur in vivo. Our simulations show that adsorption is a fast and irreversible process which
are not found to contribute much to adsorption energy. Surfaces with different degrees of hydrophobicity
is accompanied by partial unfolding. The results and the thermodynamic analysis presented here are
consistent with and rationalize previous experimental work.
